Foreword

Gregory T. Carter, MD

Department of Rehabilitation MedicineUniversity of Washington School of Medicine

Marijuana is a colloquial term used to refer to the dried flowers of the female Cannabis Sativa and Cannabis Indica plants. Marijuana, or cannabis, as it is more appropriately called, has been part of humanity's medicine chest for almost as long as history has been recorded.

All forms of cannabis plants are quite complex, containing over 400 chemicals. Approximately 60 of these chemicals are classified as cannabinoids. Among the most psychoactive of the cannabinoids is delta-9-tetrahydrocannabinol (THC), the active ingredient in the prescription medications dronabinol (Marinol) and naboline (Cesamet). Other major cannabinoids include cannabidiol (CBD) and cannabinol (CBN), both of which are non-psychoactive but possess distinct pharmacological effects.

Cannabis was formally introduced to the United States Pharmacopoeia (USP) in 1854, though written references regarding the plant's therapeutic use date back as far as 2800 B.C. By 1900, cannabis was the third leading active ingredient, behind alcohol and opiates, in patent medicines for sale in America. However, following the Mexican Revolution of 1910, Mexican immigrants flooded into the United States, introducing to American culture the recreational use of marijuana. Anti-drug campaigners warned against the encroaching, so-called "Marijuana Menace," and alleged that the drug's use was responsible for a wave of serious, violent criminal activity. In 1937, after testimony from Harry Anslinger -- a strong opponent of marijuana and head of the Federal Bureau of Narcotics in the 1930s -- and against the advice of the American Medical Association, the Marijuana Tax Act was pushed through Congress, effectively outlawing all possession and use of the drug.

At the time of the law's passage, there were no fewer than 28 patented medicines containing cannabis available in American drug stores with a physician's prescription.

These cannabis-based medicines were produced by reputable drug companies like Squibb, Merck, and Eli Lily, and were used safely by tens of thousands of American citizens. The enactment of the Marijuana Tax Act abruptly ended the production and use of medical cannabis in the United States, and by 1942 cannabis was officially removed from the Physician's Desk Reference.

Fortunately, over the past few decades there has been a significant rebirth of interest in the viable medical uses of cannabis. Much of the renewed interest in cannabis as a medicine lies not only in the drug's effectiveness, but also in its remarkably low toxicity. Lethal doses in humans have not been described. This degree of safety is very rare among modern medicines, including most over-the-counter medications. As a result, the National Institutes of Health (NIH), the National Academy of Sciences Institute of Medicine, and even the US Food and Drug Administration have all issued statements calling for further investigation into the therapeutic use of cannabis and cannabinoids.

The discovery of an endogenous cannabinoid system, with specific receptors and ligands, has progressed our understanding of the therapeutic actions of cannabis from folklore to valid science. It now appears that the cannabinoid system evolved with our species and is intricately involved in normal human physiology -- specifically in the control of movement, pain, reproduction, memory, and appetite, among other biological functions. In addition, the prevalence of cannabinoid receptors in the brain and peripheral tissues suggests that the cannabinoid system represents a previously unrecognized ubiquitous network in the nervous system.

Cannabinoid receptor sites are now known to exist in the nervous systems of all animals more advanced than hydra and mollusks. This is a result of at least 500 million years of evolution. The human body's neurological, circulatory, endocrine, digestive, and musculoskeletal systems have now all been shown to possess cannabinoid receptor sites. Indeed, even cartilage tissue has cannabinoid receptors, which makes cannabis a prime therapeutic agent to treat osteoarthritis. Cannabinoids have been shown to produce an anti-inflammatory effect by inhibiting the production and action of tumor necrosis factor (TNF) and other acute phase cytokines, which also makes them ideal compounds to treat the autoimmune forms of arthritis. It is now suggested by some researchers that these widely spread cannabinoid receptor systems are the mechanisms by which the body maintains homeostasis (the regulation of cell function), allowing the body's tissues to communicate with one another in this intricate cellular dance we call "life." With this knowledge of the widespread action of cannabinoids within all these bodily systems, it becomes much easier to conceptualize how the various forms of cannabinoids might have a potentially therapeutic effect on diseases ranging from osteoarthritis to amyotrophic lateral sclerosis (ALS).

Another one of the exciting therapeutic areas that cannabis may impact is chronic pain. Cannabinoids produce analgesia by modulating rostral ventromedial medulla neuronal activity in a manner similar to, but pharmacologically distinct from, that of morphine. This analgesic effect is also exerted by some endogenous cannabinoids (anandamide) and synthetic cannabinoids (methanandamide). Ideally, cannabinoids could be used alone or in conjunction with opioids to treat people with chronic pain, improve their quality of life and allow them to return to being a productive citizen.

When discussing the therapeutic use of cannabis and cannabinoids, opponents inevitably respond that patients should not smoke their medicine. Patients no longer have to. Medical cannabis patients who desire the rapid onset of action associated with inhalation, but who are concerned about the potential harms of noxious smoke eliminate their intake of carcinogenic compounds by engaging in vaporization rather than smoking. Cannabis vaporization limits respiratory toxins by heating cannabis to a temperature where cannabinoid vapors form (typically around 180-190 degrees Celsius), but below the point of combustion where noxious smoke and associated toxins (e.g., carcinogenic hydrocarbons) are produced (near 230 degrees Celsius). This eliminates the inhalation of any particulate matter and removes the health hazards of smoking. In clinical trials, vaporization has been shown to safely and effectively deliver pharmacologically active, aerosolized cannabinoids deeply into the lungs, where the rich vascular bed will rapidly deliver them to tissues throughout the body.

The following report summarizes the most recently published scientific research on the therapeutic use of cannabis and cannabinoids for more than a dozen diseases, including Alzheimer's, amyotrophic lateral sclerosis, diabetes, hepatitis C, multiple sclerosis, rheumatoid arthritis, and Tourette's syndrome. It is my hope that readers of this report will come away with a fair and balanced view of cannabis -- a view that is substantiated by scientific studies and not by anecdotal opinion or paranoia. Cannabis is neither a miracle compound nor the answer to everyone's ills. However, it does appear to have remarkable therapeutic benefits that are there for the taking if the governmental barriers for more intensive scientific study are removed.

The cannabis plant does not warrant the tremendous legal and societal commotion that has occurred over it. Over the past 30 years, the United States has spent billions in an effort to stem the use of illicit drugs, particularly marijuana, with limited success. Many very ill people have had to fight long court battles to defend themselves for the use of a compound that has helped them. Rational minds need to take over the war on drugs, separating myth from fact, right from wrong, and responsible medical use from other less compelling behavior.

The medical marijuana user should not be considered a criminal in any state. Most major medical groups, including the Institute of Medicine, agree that cannabis is a compound with significant therapeutic potential whose "adverse effects ... are within the range of effects tolerated for other medications." Over a decade ago, the Drug Enforcement Administration (DEA) studied the medical properties of cannabis. After considerable study, DEA Administrative Law Judge Francis L. Young concluded: "The evidence clearly shows that marijuana is capable of relieving the distress of great numbers of very ill people, and doing so with safety under medical supervision. ... It would be unreasonable, arbitrary and capricious for the DEA to continue to stand between those sufferers and the benefits of this substance."

Despite this conclusion, over a decade later the DEA and the rest of the federal government persist in their policy of total prohibition. Nevertheless, the scientific process continues to evaluate the therapeutic effects of cannabis through ongoing research and assessment of available data. With regard to the medical use of cannabis, our legal system should take a similar approach, using science and logic as the basis of policy making rather than relying on political rhetoric and false perceptions regarding the alleged harmful effects of recreational marijuana use.